ARC-1013 | 1106998-42-8

• 分子结构分类: 有机化合物
• 英文名称: ARC-1013
• 英文别名: 6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1S)-2-(4-benzoylphenyl)-1-carbamoylethyl]hexanamide；(2S,3S,4R,5R)-N-[6-[[(2S)-1-amino-3-(4-benzoylphenyl)-1-oxopropan-2-yl]amino]-6-oxohexyl]-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carboxamide
• CAS: 1106998-42-8
• 化学式: C₃₂H₃₆N₈O₇
• 分子量: 644.687
• InChiKey: CZIYSJFBJRVVDO-DRXVFNRASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  47
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  238
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  在 三异丙基硅烷 、 三氟乙酸 作用下， 以 水 为溶剂， 反应 2.5h， 生成 ARC-1013
  参考文献：
  名称：

  Structural Analysis of ARC-Type Inhibitor (ARC-1034) Binding to Protein Kinase A Catalytic Subunit and Rational Design of Bisubstrate Analogue Inhibitors of Basophilic Protein Kinases

  摘要：

  The crystal structure of a complex of the catalytic subunit (type alpha) of cAMP-dependent protein kinase (PKA C alpha) with ARC-type inhibitor (ARC-1034), the presumed lead scaffold of previously reported adenosine-oligo-arginine conjugate-based (ARC-type) inhibitors, was solved. Structural elements important for interaction with the kinase were established with specifically modified derivatives of the lead compound. On the basis of this knowledge, a new generation of inhibitors, conjugates of adenosine-4'-dehydroxymethyl-4'-carboxylic acid moiety and oligo(D-arginine), was developed with inhibitory constants well into the subnanomolar range. The structural determinants of selectivity of the new compounds were established in assays with ROCK-II and PKB gamma.

  DOI：

  10.1021/jm800797n